Prediction of cis-regulatory elements controlling genes differentially expressed by retinal and choroidal vascular endothelial cells

Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two endothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p < 0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., glucocorticoid receptor, high mobility group AT-hook 1, heat shock transcription factor 1, p53, vitamin D receptor) or choroidal (i.e., transcription factor E2F, Yin Yang 1, zinc finger 5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy

Predictors of Change Following Cognitive-Behavioral Treatment of Children with Anxiety Problems: A Preliminary Investigation on Negative Automatic Thoughts and Anxiety Control

The purpose of the present study was to evaluate negative automatic thoughts and anxiety control as predictors of change produced by cognitive-behavioral treatment of youths with anxiety disorders. Forty-five high-anxious children aged between 9 and 12 years who were selected from the primary school population, received a standardized CBT intervention that was provided in a group format. Before and after the intervention, children completed scales of negative automatic thoughts and perceived control over anxiety-related events as well as a questionnaire for measuring DSM-defined anxiety disorders symptoms, which was the outcome measure. Results indicated that CBT was effective in reducing children’s anxiety symptoms. Most importantly, the reduction of anxiety disorders symptoms was significantly associated with a decrease in negative automatic thoughts and an increase of anxiety control, which provides support for the notion that these variables are candidate mediators of CBT in anxious youths

Disclosure of distress among anxiety-disordered youth: Differences in treatment outcome

The present study evaluated treatment outcome differences in anxiety-disordered youth who differed in their disclosure of internal distress as measured in a structured diagnostic interview. One hundred and seventy-one clinic-referred, anxiety-disordered children served as participants. Participants\u27 primary diagnoses were one of three anxiety disorders: separation anxiety, generalized anxiety/overanxious, or social phobia/avoidance. At a pretreatment assessment, children and their parents were interviewed separately using the Anxiety Disorders Interview Schedule (ADIS) to determine the child\u27s diagnosis. The child\u27s status as a discloser of high distress or discloser of low distress was determined by the parents\u27 endorsement of an anxiety disorder and the child\u27s endorsement or lack of endorsement of an anxiety disorder, respectively. Parents, teachers, and children also completed measures assessing the child\u27s psychopathology (e.g., Revised Children\u27s Manifest Anxiety Scale, Child Behavior Checklist). In general, findings indicated that the level of distress reported by the children moderated treatment outcome. Although both groups benefited from treatment, the children disclosing high distress experienced greater treatment gains than the children disclosing low distress. © 2004 Elsevier Inc. All rights reserved

Effectiveness and underlying mechanisms of a group-based cognitive behavioural therapy-based indicative prevention program for children with elevated anxiety levels

Contains fulltext : 116470.pdf (publisher's version ) (Open Access)Background Anxiety is a problem for many children, particularly because of its negative consequences not only on the wellbeing of the child, but also on society. Adequate prevention and treatment might be the key in tackling this problem. Cognitive behavioural therapy (CBT) has been found effective for treating anxiety disorders. “Coping Cat” is one of the few evidence-based CBT programs designed to treat anxiety symptoms in children. The main aim of this project is to conduct a Randomized Controlled Trial (RCT) to evaluate the effectiveness of a Dutch version of Coping Cat as an indicative group-based prevention program. The second aim is to gain insight into the mechanisms underlying its effectiveness. Methods/design Coping Cat will be tested in Dutch primary school children grades five through eight (ages 7 to 13) with elevated levels of anxiety. This RCT has two conditions: 130 children will be randomly assigned to the experimental (N=65, Coping Cat) and control groups (N=65, no program). All children and their mothers will be asked to complete baseline, post intervention, and 3-month follow-up assessments. In addition, children in both the experimental and control group will be asked to complete 12 weekly questionnaires matched to the treatment sessions. Main outcome measure will be the child’s anxiety symptoms level (SCAS). Four potential mediators will be examined, namely active coping, positive cognitive restructuring, self efficacy and cognitions about ones coping ability (from now on coping cognitions). Discussion It is hypothesized that children in the experimental condition will experience reduced levels of anxiety in comparison with the control group. Further, active coping, positive cognitive restructuring, and coping cognitions are expected to mediate program effectiveness. If Coping Cat proves effective as a prevention program and working mechanisms can be found, this group-based approach might lead to the development of a cost-effective program suitable for prevention purposes that would be easily implemented on a large scale.7 p

Therapy for youths with anxiety disorders: A second randomized clinical trial

Ninety-four children (aged 9-13 years) with anxiety disorders were randomly assigned to cognitive behavioral treatment or waiting-list control. Outcomes were evaluated using diagnostic status, child self-reports, parent and teacher reports, cognitive assessment and behavioral observation; maintenance was examined using 1-year follow-up data. Analyses of dependent measures indicated significant improvements over time, with the majority indicating greater gains for those receiving treatment. Treatment gains returned cases to within nondeviant limits (i.e., normative comparisons) and were maintained at 1-year follow-up. Client age and comorbid status did not moderate outcomes. A preliminary examination of treatment segments suggested that the enactive exposure (when it follows cognitive educational training) was an active force in beneficial change. Discussion includes suggestions for future research